title: Tendon and skeletal muscle matrix gene expression and functional responses to immobilisation and rehabilitation in young males: effect of growth hormone administration.
abstract: We examined the effect of growth hormone (GH) on connective tissue of tendon and skeletal muscle during immobilisation and re-training in humans. Young men (20-30 years; n = 20) were randomly assigned to daily recombinant human GH (rhGH) (33-50 μg kg(-1) day(-1)) or placebo (Plc), and had one leg immobilised for 2 weeks, followed by 6 weeks of strength training. The cross-sectional area (CSA), maximal muscle strength (maximal voluntary contraction, MVC) and biomechanical properties of the quadriceps muscle and patellar tendon were determined. Muscle and tendon biopsies were analysed for mRNA of collagen (COL1A1/3A1), insulin-like growth factors (IGF-1Ea/Ec), lysyl oxidase (LOX), matrix metalloproteases (MMP-2 and MMP-9), decorin and tenascin-C. Fibril morphology was analysed by transmission electron microscopy (TEM) to detect changes in the fibril diameter distribution. In muscle, CSA and MVC declined with immobilisation and recovered with rehabilitation similarly in both groups. Likewise, both groups showed increased IGF-1Ea/Ec and COL1A1/3A1 expression in muscle during re-training after immobilisation compared with baseline, and the increase was more pronounced when subjects received GH. The tendon CSA did not change during immobilisation, but increased in both groups during 6 weeks of rehabilitation (∼14%). A decline in tendon stiffness after immobilisation was observed only in the Plc group, and an increase during 6 weeks of rehabilitation was observed only in the GH group. IGF-1Ea and COL1A1/3A1 mRNA increased with immobilisation in the GH group only, and LOX mRNA was higher in the GH group than in the Plc group after immobilisation. Both groups showed an increase in MMP-2 with immobilisation, whereas no changes in MMP-9, decorin and tenascin-C were observed. The tendon fibril diameter distribution remained unchanged in both groups. In conclusion, GH stimulates collagen expression in both skeletal muscle and tendon, abolishes the normal inactivity-related decline in tendon stiffness and LOX, and results in increased tendon CSA and stiffness during rehabilitation. GH has a matrix-stabilising effect during periods of inactivity and rehabilitation in humans.
authors.affiliation: A. P. Boesen: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark. boesenanders@hotmail.com.
authors.forename: A P
authors.initials: AP
authors.lastname: Boesen
authors.forename: K
authors.initials: K
authors.lastname: Dideriksen
authors.forename: C
authors.initials: C
authors.lastname: Couppé
authors.forename: S P
authors.initials: SP
authors.lastname: Magnusson
authors.forename: P
authors.initials: P
authors.lastname: Schjerling
authors.forename: M
authors.initials: M
authors.lastname: Boesen
authors.forename: M
authors.initials: M
authors.lastname: Kjaer
authors.forename: H
authors.initials: H
authors.lastname: Langberg
mesh_terms: D000328:Adult; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D019382:Human Growth Hormone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007103:Immobilization / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D035002:Lower Extremity / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D010329:Patella / Q000502:physiology; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D011859:Radiography; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D013710:Tendons / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D055815:Young Adult
chemical_list: C439971:COL3A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; C583557:IGF1 protein, human; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D008249:Protein-Lysine 6-Oxidase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2